Research progress of β-adrenergic receptor antagonists in the treatment of ocular neovascular diseases / 中华眼底病杂志

Ocular neovascularization is a pathological change in various ocular diseases such as diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion and age-related macular degeneration, which seriously affects patient's vision. β receptors are expressed in conjunctiva, corneal epithelial cells, corneal endothelial cells, extraocular muscles, trabecular meshwork, ciliary muscle, lens and retina. β adrenergic receptor antagonists bind to β receptors to exert anti-angiogenic effects by inhibiting the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1, interleukin-6 and other angiogenic cytokines; reducing macrophage-related inflammatory response; increasing the expression of anti-angiogenic factors. In the treatment of corneal neovascularization, choroidal neovascularization, and retinopathy of prematurity, it can significantly reduce the area of neovascularization and delay disease progression. Co-administration of anti-VEGF drugs can reduce the frequency of administration of anti-VEGF drugs. At effective therapeutic concentrations, β-adrenergic receptor antagonists are well tolerated; they have broader targets than anti-VEGF drugs, which offers new treatment strategies for ocular neovascularization such as corneal, choroidal and retinal neovascularization.

Prescription profile of antiarrhythmic drugs in a group of patients in Colombia / Perfil de prescripción de fármacos antiarrítmicos en un grupo de pacientes en Colombia

Abstract Objective: To determine the prescription patterns of antiarrhythmic drugs and variables associated with their use in a population of patients affiliated with the Colombian Health System. Methods: A cross-sectional study was performed on a population database with patients who received antiarrhythmics from March to May 2016. Sociodemographic, pharmacological and comedication variables were included. SPSS-24 was used for data analysis using X2 tests and multivariate analyses. Results: In total, 2772 patients were treated with antiarrhythmics in the evaluated period. The mean age was 70.1 ± 13.1 years, and 51.2% were women. In total, 79.4% used a β-blocker, 58.5% amiodarone and 2.9% a calcium channel blocker. Moreover, 1192 (43.0%) patients were prescribed a single antiarrhythmic, and 1580 (57.0%) received two or more. There were 2603 patients (93.9%) with comedication, including lipid-lowering drugs (62.6%), inhibitors of the renin angiotensin aldosterone system (62.6%) and antiplatelet drugs (42.0%). Age older than 65 years increased the probability of comedication (odds ratio [OR]: 2.48; 95% confidence interval [95% CI]: 1.59-3.85), and the risk was proportional to age. We identified 1364 patients treated with conditional risk medications for QT prolongation (49.2%), 68 with a possible risk (2.5%) and 171 (6.2%) with a known risk. Conclusion: Antiarrhythmic drugs recommended by clinical practice guidelines are mainly used; however, risk interactions interactions of QT prolongation were identified and should be taken into account by physicians to avoid adverse events or complications.

Resumen Objetivo: determinar los patrones de prescripción de fármacos antiarrítmicos y variables asociadas a su utilización en una población de pacientes afiliados al sistema de salud de Colombia. Métodos: estudio de corte transversal sobre una base de datos poblacional con pacientes que recibieron antiarrítmicos entre marzo y mayo de 2016. Se incluyeron variables sociodemográficas, farmacológicas y de comedicación. Para el análisis de datos se utilizó SPSS-24, realizando pruebas X2 y análisis multivariado. Resultados: se encontraron 2 772 pacientes en tratamiento con antiarrítmicos en el periodo evaluado, la edad promedio fue 70,1 ± 13,1 años, 51,2 % eran mujeres. El 79,4% utilizó algún β-bloqueador, 58,5% amiodarona y 2,9 % algún bloqueante de canales de calcio. Al 43 % se les prescribió un solo antiarrítmico y 57 % recibieron dos o más. El 93,9 % tenía con alguna comedicación, especialmente hipolipemiantes (62,6 %), inhibidores del sistema renina angiotensina aldosterona (62,6 %) y antiagregantes (42 %). Ser mayor de 65 años aumentó la probabilidad de comedicación (OR:2,48; IC95 %:1,59-3,85) y el riesgo fue proporcional al incremento de la edad. El 49,2 % (n=1364) estaban tratados con medicamentos de riesgo condicional de prolongación del QT, 2,5 % (n=68) con riesgo posible y 6,2% (n=171) de riesgo conocido. Conclusión: se están utilizando los mismos fármacos recomendados por las guías de práctica clínica; sin embargo, se encontraron interacciones de riesgo de prolongación del intervalo QT que deben ser tenidas en cuenta para evitar eventos o complicaciones en los pacientes.

Effect of beta-adrenergic receptor blockers on the risk of death in elderly patients with chronic heart failure and chronic obstructive pulmonary disease / 中华老年医学杂志

Objective:To analyze the effects of β-receptor blockers on all-cause mortality in elderly patients with mild-moderate chronic heart failure(CHF)and chronic obstructive pulmonary disease(COPD), and to analyze risk factors relevant to death.Methods:This was a multicenter retrospective cohort study from January 2013 to December 2017.The 400 elderly patients with CHF and COPD treated in Rizhao People's Hospital(187 cases), Shandong Provincial Hospital(122 cases)and Beijing Anzhen Hospital(91 cases)were enrolled.The patients receiving β-receptor blockers were included as β-receptor blockers group(n=200), and the patients matching for similar age and cardio-pulmonary function, not receiving β-receptor blockers were selected as the control group(n=200). All patients were followed up until December 31, 2019.The primary endpoints were all-cause mortality.The risk factors for all-cause death were compared and analyzed.Results:Among 400 patients, the average age was(72.2±11.7)years with 226 males(56.5%). There was no significant difference in baseline data such as age, gender ratio, body mass index, heart function, lung function, and treatment regimen after matching between the two groups(all P>0.05). At end of 3-years follow-up, risks of all-cause mortality( χ2=7.284, P<0.01), and re-hospitalization risk due to worsening heart failure( χ2=6.782, P<0.01), acute exacerbation of COPD( χ2=6.921, P<0.01)were significantly reduced in β-receptor blockers group versus control group.Multivariate Cox regression analysis showed that age ≥75 years( HR=2.142), diabetes( HR=1.929), ratio of baseline forced expiratory volume in the first second / forced vital capacity <66.8%( HR=1.114), baseline glomerular filtration rate <72.0 ml/min( HR=3.572)and left ventricular ejection fraction <46.4%( HR=2.294)at end of 3-year follow-up were risk factors for mortality, whileβ-receptor blockers( HR=0.745)was a protective factor(all P<0.05). Conclusions:β-receptor blockers can significantly reduce the mortality and re-hospitalization rate in elderly patients with CHF and COPD.

NO CENÁRIO ATUAL, QUAL O PAPEL DOS BETABLOQUEADORES NO TRATAMENTO DA HIPERTENSÃO? / IN THE CURRENT SCENARIO, WHAT IS THE ROLE OF BETA-BLOCKERS IN THE TREATMENT OF HYPERTENSION?

As teorias sobre a existência de receptores adrenérgicos foram descritas na literatura em meados da década de 40, sendo reconhecido anos depois que a inibição do sistema nervoso simpático por um determinado composto bloqueador beta- -adrenérgico poderia beneficiar pacientes com arritmias cardíacas e angina pectoris. Nasceram aí as primeiras substâncias bloqueadoras beta adrenérgicas não seletivas, destacando-se o propranolol. Desde então, centenas de bloqueadores beta adrenérgicos (BB) foram sintetizados e dezenas estão disponíveis em todo o mundo para uso clínico. Os mecanismos farmacológicos dos BBs são múltiplos e variam principalmente de acordo o predomínio de ação nos receptores adrenérgicos e com a lipossolubilidade, entre outros. De maneira geral, ligam-se e produzem um antagonismo competitivo e reversível nos receptores distribuídos pelo organismo. Os principais mecanismos fisiopatológicos propostos para explicar a ação medicamentosa dos BBs na hipertensão arterial sistêmica são redução do débito cardíaco, da resistência vascular periférica, do tônus vasomotor e do volume plasmático, inibição de renina, efeitos no sistema nervoso central, melhoria na adesão vascular e redefinição dos níveis de barorreceptores. Atualmente, os BBs não são preconizados como primeira linha de tratamento de hipertensão arterial sem complicações, porém eles são particularmente úteis para o tratamento da hipertensão na presença de algumas comorbidades não cardiovasculares, como a enxaqueca e o tremor essencial. Além disso, os BBs ganham destaque especial em situações cardiovasculares específicas, como angina sintomática, taquiarritmias, pós infarto agudo do miocárdio, insuficiência cardíaca com fração de ejeção reduzida e como alternativa aos inibidores da ECA ou BRA em mulheres hipertensas mais jovens que planejam engravidar. Vale ressaltar que em algumas destas situações os BBs passam a ter indicação mandatória, mesmo que não associadas à hipertensão arterial

Theories about the existence of adrenergic receptors were described in the mid-40s, being recognized years later that inhibition of the sympathetic nervous system by a beta-adrenergic blocking compound could benefit patients with cardiac arrhythmias and angina pectoris. That's how the first non-selective beta-blocking adrenergic substances appeared, highlighting propranolol. Since then, hundreds of beta-adrenergic blockers have been synthesized and dozens are available worldwide for clinical use. The pharmacological mechanisms of BBs are multiple and vary mainly according to the predominance of action in adrenergic receptors and with liposolubility. In general, they bind and produce a competitive and reversible antagonism in the receptors distributed by the organism. The main pathophysiological mechanisms proposed to explain the action of BBs in systemic arterial hypertension are reduced cardiac output, peripheral vascular resistance, vasomotor tone and plasma volume, renin inhibition, effects on the central nervous system, improvement in vascular adherence and redefinition of baroreceptor levels. Currently, BBs are not recommended as the first line of treatment for non-complicated arterial hypertension, but they are particularly useful for the treatment of hypertension in the presence of some comorbidities, such as migraine and essential tremor. Besides that, BBs gain special prominence in specific cardiovascular situations, such as symptomatic angina, tachyarrhythmias, post-acute myocardial infarction, heart failure with reduced ejection fraction and as an alternative to ACE or ARB inhibitors in younger hypertensive women planning to become pregnant. It is worth mentioning that in some of these situations BBs are mandatory, even if not associated with arterial hypertension

Beta-Blocker Type Effect on Substrate Oxidation during HIIE in Heart Failure Patients: Pilot Data / Efeito do Tipo Betabloqueador na Oxidação de Substratos durante HIIE em Pacientes com Insuficiência Cardíaca: Dados Piloto

Abstract The effect of third and second-generation type of beta-blocker on substrate oxidation especially during high-intensity exercises are scarce. The objective of the study is to explore differences of beta-blocker regimens (vasodilating vs. non-vasodilating beta-blockers) for substrate oxidation during in high-intensity intermittent exercise (HIIE) in chronic heart failure and reduced ejection fraction (HFrEF). Eighteen CHF males (58.8 ± 9 years), 8 under use of β1 specific beta-blockers+alfa 1-blocker and 10 using β1 non-specific beta-blockers, were randomly assigned to 4 different HIIE, in a cross-over design. The 4 protocols were: 30 seconds (A and B) or 90 seconds (C and D) at 100% peak power output, with passive (A and C) or active recovery (50% of PPO; B and D). Energy expenditure (EE; kcal/min), quantitative carbohydrate (CHO) and lipid oxidation (g/min) and qualitative (%) contribution were calculated. Two-way ANOVA and Bonferroni post-hoc test were used (p-value ≤ 0.05) to compare CHO and lipid oxidation at rest and at 10min. Total exercise time or EE did not show differences for beta-blocker use. The type of beta-blocker use showed impact in CHO (%) and lipid (g/min and %) for rest and 10 min, but absolute contribution of CHO (g/min) was different just at 10min (Interaction p = 0.029). Higher CHO oxidation was found in vasodilating beta-blockers when comparing to non-vasodilating. According to our pilot data, there is an effect of beta-blocker type on substrate oxidation during HIIE, but no influence on EE or exercise total time in HFrEF patients.

Resumo Os dados sobre efeito do tipo de betabloqueador de terceira e segunda geração na oxidação do substrato, especialmente durante exercícios de alta intensidade, são escassos. O objetivo do estudo é explorar as diferenças de tratamentos com betabloqueadores (betabloqueadores vasodilatadores vs. não-vasodilatadores) na oxidação de substratos durante exercícios intermitentes de alta intensidade (HIIE) na insuficiência cardíaca crônica e fração de ejeção do ventrículo esquerdo reduzida (ICFEr). Dezoito pacientes do sexo masculino com ICC (58,8 ± 9 anos), 8 em uso de betabloqueadores β1 específicos + bloqueador α-1 e 10 utilizando betabloqueadores β1 não-específicos, foram aleatoriamente designados para 4 diferentes HIIE, em um desenho cruzado. Os 4 protocolos foram: 30 segundos (A e B) ou 90 segundos (C e D) a 100% da potência de pico de saída (PPO), com recuperação passiva (A e C) ou ativa (50% de PPO; B e D). O gasto energético (GE; kcal/min), a ingestão de carboidratos quantitativos (CHO) e oxidação lipídica (g/min) e qualitativa (%) foram calculados. Anova de dois fatores e teste post-hoc de Bonferroni foram usados (p-valor ≤ 0,05) para comparar a oxidação de CHO e lipídios em repouso e aos 10 minutos. O tempo total de exercício ou GE não mostraram diferenças de acordo com o uso de betabloqueadores. O tipo de betabloqueador mostrou impacto em CHO (%) e lípides (g/min e %) para repouso e aos 10 min, mas a contribuição absoluta de CHO (g/min) foi diferente apenas aos 10 minutos (Interação p = 0,029). Foram encontradas maiores oxidações de CHO com betabloqueadores vasodilatadores quando comparados com os não-vasodilatadores. De acordo com nossos dados piloto, há um efeito do tipo do betabloqueador na oxidação do substrato durante o HIIE, mas nenhuma influência no GE ou no tempo total de exercício nos pacientes com ICFEr.

Rol cardioprotector del carvedilol para pacientes en quimioterapia, revisión sistemática y metanálisis de estudios clínicos aleatorizados / Cardioprotective role of carvedilol in patients on chemotherapy: systematic review and meta-analysis of randomized clinical trials

Objetivo: Los tratamientos oncológicos pueden causar alteraciones cardiovasculares pese a lograr tratamientos exitosos de la enfermedad. El rol del carvedilol como cardioprotector en este escenario es incierto. Se evaluó la evidencia existente respecto al rol del carvedilol para prevenir el deterioro de la función sistólica del ventrículo izquierdo en pacientes sometidos a quimioterapia Materiales y métodos: Se trata de una revisión sistemática y metanálisis de ensayos clínicos aleatorizados. Se realizó una búsqueda en Pubmed, Embase, Cochrane, Scielo y clinicaltrials.gov; incluyendo trabajos que evaluaron y compararon la diferencia en la fracción de eyección del ventrículo izquierdo (antes y después de recibir quimioterapia) entre pacientes con y sin carvedilol. El tamaño del efecto se expresó como la diferencia estandarizada (d) y la diferencia de medias entre grupos con un intervalo de confianza del 95 %. Resultados: Se identificaron 9749 manuscritos; se incluyeron 4 estudios con un total de 343 pacientes adultos, 86.9 % de sexo femenino, con fracción de eyección del ventrículo izquierdo normal y sin historia previa de insuficiencia cardíaca. El grupo bajo tratamiento con carvedilol mostró una caída menor aunque sin diferencia estadísticamente significativa de la fracción de eyección del ventrículo izquierdo que el grupo control (d= -0.501 [ -1.372, 0.371]; p = 0.260; siendo la diferencia de la reducción de fracción de eyección del ventrículo izquierdo pre-post quimioterapia entre ambos grupos: -0.71 %[-1.88, 0.575]); sin embargo la fracción de eyección del ventrículo izquierdo final fue mayor en el grupo carvedilol (d= 0.361 [ 0.146, 0.575]; p = 0.001; siendo el tamaño del efecto = 1.73 %[0.74,2.72]. Conclusiones: El carvedilol solo o combinado, se asocia a una mayor fracción de eyección del ventrículo izquierdo, pero no a un menor descenso de la misma al finalizar la quimioterapia. Son necesarios estudios clínicos aleatorizados con mayor población, seguimiento y calidad para determinar la implicancia clínica del uso de carvedilol en pacientes sometidos a quimioterapia.

Objective: Cancer therapy may cause cardiovascular toxicity even after successful treatment. It is unknown the cardioprotective role of carvedilol in this setting. We evaluated the role of carvedilol for the prevention of left ventricular systolic dysfunction in chemotherapy patients. Materials and methods: A systematic review and meta-analysis of randomized clinical trials were performed through PubMed, Embase, Cochrane, SciELO and ClinicalTrials.gov, including trials that evaluated and compared the difference of left ventricular ejection fraction (pre- and post-chemotherapy) in patients with and without carvedilol treatment. The effect size was expressed as the standardized difference (d) and the mean difference between groups with 95 % confidence interval. Results: Nine thousand seven hundred forty-nine (9,749) manuscripts were screened. Four (4) studies consisting of a total of 343 adult patients, from which 86.9 % were females with normal left ventricular ejection fraction and no past history of heart failure, were included. The carvedilol group showed less -though not statistically significant- reduction of the left ventricular ejection fraction than the control group (d = -0.501 [-1.372, 0.371]; p = 0.260). The difference of the reduction in the left ventricular ejection fraction pre- and post-chemotherapy in both groups was -0.71 % [-1.88, 0.46]. However, left ventricular ejection fraction post-chemotherapy was higher in the carvedilol group (d = 0.361 [0.146, 0.575]; p = 0.006) and the effect size was 1.73 % [0.74, 2.72]. Conclusions: Monotherapy or combination therapy with carvedilol is associated with a higher left ventricular ejection fraction, but not with less reduction in the left ventricular ejection fraction post-chemotherapy. Long-term, larger and high-quality randomized clinical trials are required to determine the clinical implication of the use of carvedilol in patients under chemotherapy.

Impact of beta blockers on survival outcomes in ovarian cancer: a nationwide population-based cohort study / 부인종양

OBJECTIVE: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. METHODS: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. RESULTS: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ≥60 years, longer duration use (≥1 year), in patients with Charlson Comorbidity Index (CCI) ≥3, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (≥180 days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (≥720 days). In multivariate Cox proportional hazards model, longer duration of BB medication (≥1 year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. CONCLUSION: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ≥3).

Heart rate control in chronic heart failure patients received cardiovascular implantable electronic device therapy: effects of optimized medication / 中华心血管病杂志

Objective@#To investigate the heart rate control situation of chronic heart failure (CHF) patients who received cardiovascular implantable electronic device (CIED) therapy, and to assess the heart rate control efficacy by optimized medication adjustment.@*Methods@#We performed a perspective study in heart failure with reduced left ventricular ejection fraction (HFrEF) patients who received CIED according to guideline recommendations, patients were enrolled from January 2012 to January 2017. Resting heart rate (RHR) recorded by electrocardiogram after 10 minutes' rest and medication usage within 1 month were recorded at baseline. RHR less than 70 beats per minute (bpm) was regarded as well controlled. β-receptor blockers and (or) ivabradine would be added in patients whose RHR were over 70 bpm. RHR after optimized medication adjustment was recorded during follow-up period.@*Results@#One hundred and fifty patients were included in this study with average RHR (80.6±11.9) bpm. RHR was<70 bpm in 27.3% (41/150) patients at baseline and β-receptor blockers was underused in 80.7% patients (88/109) whose RHR was>70 bpm. The overall RHR decreased to (73.1±10.4) bpm and percent of patients with RHR<70 bpm increased to 70.0% (105/150) after up-titration of β-receptor blockers compared to baseline (χ2=52.958, P<0.001). Ivabradine was added in the rest 45 patients and RHR was<70 bpm in 43 out of 45 patients after ivabradine use. The overall RHR decreased to (67.1±2.7) bpm and percent of RHR<70 bpm significantly increased to 98.7% (148/150) (χ2=44.504, P<0.001 vs. up-titration of β-receptor blockers only).@*Conclusion@#RHR in CHF patients who received CIED therapy is not ideally controlled in this patient cohort, individual up-titration ofβ-receptor blockers and ivabradine use may help to optimize RHR in these patients.

Role of Soluble ST2 Levels and Beta-Blockers Dosage on Cardiovascular Events of Patients with Unselected ST-Segment Elevation Myocardial Infarction / 中华医学杂志(英文版)

<p><b>Background</b>Serum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown.</p><p><b>Methods</b>A total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI.</p><p><b>Results</b>Baseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = -0.243, P = 0.009) and LV ejection fraction (r = -0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201-8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084-3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI.</p><p><b>Conclusions</b>High baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology.</p>

Observation on effect of β-blocker in treating dilated cardiomyopathy in children / 重庆医学

Objective To observe the effect of β-blocker on dilated cardiomyopathy (DCM) in children.Methods Sixty-one children cases of DCM in this hospital from 1995 to 2015 were retrospectively analyzed and divided into the treatment group(taking β-blocker,n=35) and control group(non-taking β-blocker,n=26) according to whether taking β-blocker.The clinical effect of β-blocker was preliminarily observed.Results The heart rate,LVDD,LVSD and LA after treatment in the treatment group were significantly decreased compared with before treatment(P＜0.05),while EF was significantly increased(P＜0.05);LVDD after treatment in the control group was significantly decreased(P＜0.05),while hear rate,RV,LVDD,LVSD,LA,MV and EF had no obvious change compared with before admission(P＞0.05).The heart rate,LVDD,LVSD and EF after treatment had statistical difference between the treatment group and control group (P＜0.05),the heart function after treatment in the treatment group was significantly improved compared with the control group (P＜0.05).The heart function improvement degree after treatment in the patients with hypertension of the treatment group was significantly better than those with normal blood pressure(P＜0.05).DCM with hypertension was significantly improved after treatment and was better than DCM without hypertension (P＜0.05).The The heart function improvement degree after treatment in the patients with carvedilol treatment was obviously better than that in the patients with metoprolol treatment(P＜0.05).Conclusion β-blocker could be used in the treatment of DCM,its effect is especially good in DCM children patients with hypertension,in which the effect of carvedilol is better than that of metoprolol.

Efficacy of β-blocker in Hypertension Patients With Different Basic Heart Rate / 中国循环杂志

Objective: To explore the effect of β-blocker in hypertension patients with different basic heart rate (HR). Methods: A total of 191 hypertension patients without using β-blocker were enrolled. Based on different basic HR, the patients were divided into 3 groups: Group A: HR (70-79) beats/min, n=58, Group B: HR (80-89) beats/min, n=90 and Group C: HR≥90 beats/min, n=43. All patients received metoprolol extended release at 47.5 mg/d for 2 weeks, for those didn't reach the target HR, 23.75 mg/d was added as 71.25 mg/d for 4 weeks, for those still didn't reach target HR, the dose was added to 95 mg/d, total length of medication was 8 weeks. Blood pressure (BP) and HR were measured every 2 weeks in all patients. Results: 62％ patients had basic HR>80 beats/min, 36％ had basic HR>85 beats/min and 20％ had basic HR>90 beats/min. The average dose of metoprolol was (59.7±17.0) mg/d. HR decreased in 3 groups after medication, all P<0.05. The reducing level in Group C was (29.3±7.8) beats/min, in Group B was (18.7±4.9) beats/min and in Group A was (11.0±4.0) beats/min, P<0.05; upon HR elevating 10 beats/minute, metoprolol caused HR reducing may increase 7.9％. BP was similar among 3 groups before and after medication, P>0.05. The average HR decreasing levels in patients with metoprolol 47.5 mg/d, 71.25 mg/d and 95 mg/d were (17.6±8.1) beats/min, (19.5±8.7) beats/min and (22.5±9.2) beats/min respectively; upon dose elevated to 71.25 mg/d and 95 mg/d, metoprolol caused HR reducing may increase10.8％ and 27.8％. 1 patient had sinus bradycardia and 1 had dizziness during medication, the symptoms improved by dose reducing or drug withdrawal.Conclusion: About 2/3 hypertension patients had basic HR>80 beats/min, metoprolol could cause more HR reducing in patients with the faster basic HR. Metoprolol (47.5-95) mg/d was safe and effective in hypertension patients.

Observation on effect of β-blocker in treating dilated cardiomyopathy in children / 重庆医学

Objective To observe the effect of β-blocker on dilated cardiomyopathy (DCM) in children.Methods Sixty-one children cases of DCM in this hospital from 1995 to 2015 were retrospectively analyzed and divided into the treatment group(taking β-blocker,n=35) and control group(non-taking β-blocker,n=26) according to whether taking β-blocker.The clinical effect of β-blocker was preliminarily observed.Results The heart rate,LVDD,LVSD and LA after treatment in the treatment group were significantly decreased compared with before treatment(P＜0.05),while EF was significantly increased(P＜0.05);LVDD after treatment in the control group was significantly decreased(P＜0.05),while hear rate,RV,LVDD,LVSD,LA,MV and EF had no obvious change compared with before admission(P＞0.05).The heart rate,LVDD,LVSD and EF after treatment had statistical difference between the treatment group and control group (P＜0.05),the heart function after treatment in the treatment group was significantly improved compared with the control group (P＜0.05).The heart function improvement degree after treatment in the patients with hypertension of the treatment group was significantly better than those with normal blood pressure(P＜0.05).DCM with hypertension was significantly improved after treatment and was better than DCM without hypertension (P＜0.05).The The heart function improvement degree after treatment in the patients with carvedilol treatment was obviously better than that in the patients with metoprolol treatment(P＜0.05).Conclusion β-blocker could be used in the treatment of DCM,its effect is especially good in DCM children patients with hypertension,in which the effect of carvedilol is better than that of metoprolol.

Efficacy of β-blocker in Hypertension Patients With Different Basic Heart Rate / 中国循环杂志

Objective: To explore the effect of β-blocker in hypertension patients with different basic heart rate (HR). Methods: A total of 191 hypertension patients without using β-blocker were enrolled. Based on different basic HR, the patients were divided into 3 groups: Group A: HR (70-79) beats/min, n=58, Group B: HR (80-89) beats/min, n=90 and Group C: HR≥90 beats/min, n=43. All patients received metoprolol extended release at 47.5 mg/d for 2 weeks, for those didn't reach the target HR, 23.75 mg/d was added as 71.25 mg/d for 4 weeks, for those still didn't reach target HR, the dose was added to 95 mg/d, total length of medication was 8 weeks. Blood pressure (BP) and HR were measured every 2 weeks in all patients. Results: 62％ patients had basic HR>80 beats/min, 36％ had basic HR>85 beats/min and 20％ had basic HR>90 beats/min. The average dose of metoprolol was (59.7±17.0) mg/d. HR decreased in 3 groups after medication, all P<0.05. The reducing level in Group C was (29.3±7.8) beats/min, in Group B was (18.7±4.9) beats/min and in Group A was (11.0±4.0) beats/min, P<0.05; upon HR elevating 10 beats/minute, metoprolol caused HR reducing may increase 7.9％. BP was similar among 3 groups before and after medication, P>0.05. The average HR decreasing levels in patients with metoprolol 47.5 mg/d, 71.25 mg/d and 95 mg/d were (17.6±8.1) beats/min, (19.5±8.7) beats/min and (22.5±9.2) beats/min respectively; upon dose elevated to 71.25 mg/d and 95 mg/d, metoprolol caused HR reducing may increase10.8％ and 27.8％. 1 patient had sinus bradycardia and 1 had dizziness during medication, the symptoms improved by dose reducing or drug withdrawal.Conclusion: About 2/3 hypertension patients had basic HR>80 beats/min, metoprolol could cause more HR reducing in patients with the faster basic HR. Metoprolol (47.5-95) mg/d was safe and effective in hypertension patients.

Hypertension and Male Fertility

As the age of paternity rises in the developed world, issues of chronic disease may affect prospective fathers. Given the high prevalence of hypertension, researchers have begun to explore the relationship between hypertensive disease and male fertility. The current literature suggests an association between hypertension and semen quality. The use of various antihypertensive medications has also been linked to impaired semen parameters, making it difficult to discern whether the association exists with hypertension or its treatment. Further investigation is warranted to determine whether the observed associations are causal.

Remodelamento reverso do átrio esquerdo após terapia com carvedilolem pacientes com ICFER / Reverse left atrial remodeling after treatment with carvedilol in patients with HFREF

Fundamentos: Metade dos pacientes com fração de ejeção reduzida tem disfunção diastólica associada e os dados relacionados ao impacto da terapia com carvedilol nesses pacientes ainda são conflitantes.Objetivo: Avaliar o comportamento dos índices ecocardiográficos, cintilográficos e do volume do átrio esquerdo(VAE) antes e após três meses de terapia com carvedilol em pacientes com ICFER, classe funcional (CF) II e III da New York Heart Association (NYHA).Métodos: Selecionados 19 pacientes com IC, CF II e III, fração de ejeção <45% (método de Simpson) e sem terapiaprévia com carvedilol. Para análise estatística, utilizados os testes de Wilcoxon e McNemar, coeficiente de Spearmane regressão linear múltipla. Resultados: Houve melhora significativa dos parâmetros de função sistólica do ventrículo esquerdo (VE): DSF,VSF, FEJ Simpson, FEVI. Não houve melhora significativa dos parâmetros de função diastólica derivados do Doppler: E’, E/E’, VP, E/VP. O comportamento da função diastólica através VAE apresentou significativa melhora:VAE (83,2±33,4mL vs. 73,7±29,8mL, p=0,009), índice de VAE (44,8±15,8mL/m² vs. 39,7±14,5mL/m², p=0,014). Conclusões: A regressão do VAE após terapia em curto prazo com carvedilol não se associou à melhora dos demais índices de função diastólica, entretanto houve associação com a melhora da função sistólica do VE. Estes achados sugerem que a redução do VAE seja secundária à melhora da performance sistólica.

Background: Half of the patients with reduced ejection fraction have diastolic dysfunction associated and the data related to the impact of carvedilol therapy in these patients are still conflicting.Objective: To evaluate the behavior of echocardiographic, scintigraphic and left atrial volume (LAV) indexes before and after three months of therapy with carvedilol in patients with HFREF, New York Heart Association (NYHA) functional class (FC) II and III. Methods: Nineteen patients with HF, CF II and III, ejection fraction <45% (Simpson method) without previous therapy with carvedilol were selected. For statistical analysis, Wilcoxon and McNemar tests, Spearman coefficient and multiple linear regression were used. Results: There was significant improvement in the left ventricular (LV) systolic function parameters: DSF, ESV, Simpson EF,EFVI. There was no significant improvement in the diastolic function parameters derived from Doppler: E’, E/E’, VP, E/VP. Diastolic function behavior through VAE showed significant improvement: LAV (83.2±33.4 mL vs. 73.7±29.8 mL, p=0.009), LAV index(44.8±15.8mL/m2 vs. 39.7±14.5mL/m2, p=0.014). Conclusions: LAV regression after short-term therapy with carvedilol was not associated with improvement in other diastolic function indexes, but was associated with improved LV systolic function. These findings suggest that LAV reduction is secondary to improvement in systolic performance.

Effect of silodosin, an alpha1a-adrenoceptor antagonist, on benign prostatic hyperplasia in rat / 中国医师杂志

Objective To investigate the effect of silodosin,a selective alpha1 a-adrenoceptor antagonist on a rat model of testosterone-induced benign prostatic hyperplasia (BPH) and its mechanisms.Methods The rats were divided into three groups:control,testosterone-induced BPH,and silodosin +BPH groups.BPH was induced by subcutaneous injection of testosterone [20 mg/(kg · d)] for 4 weeks.Meanwhile silodosin + BPH groups rats were administered silodosin 4 weeks [100 μg/(kg · d)].After 4 weeks,all animals were sacrificed to examine the blood biochemical profiles,prostate volume,weight,histopathological changes,and epidermal growth factor receptor (EGFR) and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 2 (BCL-2) protein expressions.Results Each group showed an increase compared to their initial body weight;however,differences in weight change between groups were not significant (P ＞ 0.05).The BPH group displayed lower glucose levels than the control group.The serum levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were not significantly different among groups (P ＞ 0.05).The group treated with silodosin showed significantly lesser prostate size and weight than the testosterone-induced BPH group [volume:(0.93 ± 0.14) cm3 vs (1.75 ± 0.15)cm3,P ＜0.01;weight:(0.97 ±0.06)g vs (1.30±0.05)g,P ＜0.01].In addition,silodosin decreased the expressions of EGFR and BCL-2 in prostate tissues (P ＜ 0.05).Conclusions These results suggest that silodosin suppress the development of BPH by inhibiting the expressions of EGFR and BCL-2.

Therapeutic effect and its mechanism of antioxidant taurine plus metoprolol on elderly spontaneously hypertensive rats / 中华老年医学杂志

Objective To investigate the protective effects of antioxidant taurine plus metoprolol on the blood pressure(BP)and blood vessel function of elderly spontaneously hypertensive rats(SHR).Methods SHRs were divided into three groups (6 rats,each):metoprolol group (100 mg · kg-1 · d-1,intragastric administration);taurine group (200 mg · kg-1 · d-1,intraperitoneal injection);taurine plus metoprolol group(metoprolol 100 mg· kg-1 · d-1,intragastric administration ± taurine 200 mg· kg-1 · d-1,intraperitoneal injection).The control group[6 Wistar-Kyoto(WKY) rats]was treated with the same volume of sterile normal saline on the same schedule in intragastric administration and intraperitoneal injection.Blood pressure variability(BPV),diurnal variation of BP,the level of glutathion peroxidase (GSH-Px),malonaldehyde (MDA) and the aorta GSTM1 enzyme expression were evaluated before and 14 days after treatment.Results The serum GSH-Px activities were higher in metoprolol group[(2 759.8 ± 117.6) kU/L],taurine group [(2 848.0 ± 280.2) kU/L] and taurine plus metoprolol group[(3 052.8±283.7)kU/L]than in control group[(2 368.0± 60.4) kU/L] (all P＜0.05).Fourteen days after treatment,MDA level was significantly lower in taurine group[(9.5±0.7)ng/L,P＜0.01]than in control group[(13.7±1.5)ng/L].However,there was no statistical difference in MDA level between metoprolol group/taurine plus metoprolol group and control group.Forty weeks after treatment with taurine,GSTM1 protein expression was increased,but it had no statistical difference.Conclusions The combined antioxidant taurine and metoprolol can effectively decrease BPV of elderly SHRs,in which the antioxidant effect might be associated with elevated GSTM1 protein expression.

Divergencias entre guías de 2013 y 2014 de la hipertensión arterial: Posición de la Sociedad Centroamericana y del Caribe de Hipertensión y Prevención Cardiovascular¹ / Differences between the 2013 and 2014 hypertension guidelines: Position of the Central American and Caribbean Society for Hypertension and Cardiovascular Prevention

Entre finales de 2013 y principios de 2014 se publicaron las guías de hipertensión arterial (HTA) más influyentes a nivel internacional. Aunque no existen grandes diferencias entre ellas, hay discrepancias que pueden repercutir en el tratamiento y el pronóstico de las personas con hipertensión. En este artículo se analizan los principales elementos polémicos de estas guías y se emiten las recomendaciones de la Sociedad Centroamericana y del Caribe de Hipertensión y Prevención Cardiovascular sobre el tema. Las principales divergencias se centran en la categoría de prehipertensión arterial, el uso del riesgo cardiovascular global en la decisión de iniciar el tratamiento antihipertensivo, la vigencia de los betabloqueantes como medicamentos de primera línea en el tratamiento de la HTA no complicada, y el aumento del objetivo terapéutico de mantener las cifras de tensión arterial entre < 140/90 mmHg y < 150/90 mmHg en pacientes mayores de 60 años de edad, sin antecedentes personales de diabetes ni de enfermedad renal crónica. Se analizan críticamente todos los factores a favor y en contra de aceptar cada uno de estos cuatro elementos controvertidos y se incluyen los comentarios que sobre ellos ha realizado la Sociedad. Se concluye que todos los elementos polémicos de las guías de la HTA tienen elementos a favor y en contra. Sin embargo, el peso de la evidencia o el juicio clínico están a favor de subdividir la prehipertensión (Grado I y II), buscar la meta terapéutica de mantener la tensión sistólica de < 140 mmHg en todos los hipertensos de menos de 80 años de edad, mantener a los betabloqueantes como medicamentos de primera línea en la HTA no complicada, y no demorar el inicio del tratamiento farmacológico de la HTA Grado I de bajo riesgo cardiovascular global. Finalmente, se incluyen siete recomendaciones de la Sociedad basadas en los análisis realizados.

Between the end of 2013 and the beginning of 2014 the most internationally influential hypertension guidelines were published. Although there are no major differences between them, there are discrepancies that can have an impact on treatment and prognosis for individuals with hypertension. This article analyzes the main controversial elements in the guides and presents the recommendations of the Sociedad Centroamericana y del Caribe de Hipertensión y Prevención Cardiovascular (Caribbean Society for Hypertension and Cardiovascular Prevention). The main differences are found a) in the categorization of prehypertension, b) in the use of global cardiovascular risk in the decision to begin antihypertensive treatment, c) in the validity of beta-blockers as first-line drugs in treating uncomplicated hypertension, and d) the increase in the therapeutic goal of maintaining values between < 140/90 and < 150/90 mmHg in patients over 60 years of age with no history of diabetes or chronic kidney disease. All the factors in favor of and against accepting each of these four controversial criteria are analyzed critically and the observations made by the Society are included. The conclusion is that there are pros and cons for all controversial elements in the hypertension guides. However, the weight of the evidence and clinical judgment favor subdividing prehypertension into stages I and II, seeking a therapeutic goal of maintaining systolic blood pressure below 140 mmHg in all the hypertensive patients under 80 years of age, retaining beta-blockers as first-line drugs in uncomplicated hypertension, and not delaying the start of drug treatment for hypertension stage I with low global cardiovascular risk. Finally, seven recommendations by the Society based on the analysis are included.

Effect of esmolol on fluid responsiveness and hemodynamic parameters in patients with septic shock / 中华危重病急救医学

Objective To study the effects of esmolol on fluid responsiveness and hemodynamic parameters in patients with septic shock.Methods A prospective self-control study was conducted.Fifteen septic shock patients undergoing mechanical ventilation admitted to Department of Critical Care Medicine of Yijishan Hospital from January 2015 to August 2015 were enrolled.All patients enrolled in this study were given the treatment based on American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus 2012.Esmolol was intravenously injected at a beginning rate of 6 mg·kg-1·h-1, and then the dose was adjusted to reduce heart rate by 10％ from baseline.The changes in hemodynamic and systemic oxygen metabolism indexes were monitored by pulse indicator continuous cardiac output (PiCCO) before and 2 hours after the esmolol administration, and the fluid responsiveness was evaluated by stroke volume variation (SVV).SVV ≥ 10％ was considered to be a positive fluid responsiveness.Results In 15 patients, 9 were male and 6 female, with an age of 65 ± 16.Among them 10 patients suffered from pulmonary infection, and 5 patients with abdominal infection.Acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score was 21 ±9;sequential organ failure score (SOFA) was 8 ±4.28-day mortality was 40.0％.SVV was significantly decreased after esmolol infusion as compared with baseline [(14 ± 5)％ vs.(17 ±7)％, t =2.400, P =0.031].Heart rate [HR (bpm): 100±4 vs.112±8, t =8.161, P =0.000], cardiac output [CO (L/min):6.13 ± 1.45 vs.7.88 ± 1.82, t =4.046, P =0.001], cardiac index [CI (mL·s-1·m-2): 51.51 ± 11.00 vs.66.18 ± 11.48, t =4.131, P =0.001], stroke volume index [SVI (mL/m2): 31.0 ± 6.4 vs.35.4 ± 6.5, t =2.577, P =0.020], the maximum rate of left ventricular pressure rise [dp/dt max (mmHg/s): 927±231 vs.1 194±294, t =3.775, P =0.002], global ejection fraction (GEF: 0.21 ±0.05 vs.0.24±0.06, t =3.091, P =0.008), cardiac function index (CFI: 5.03 ± 1.37 vs.6.59 ± 1.92, t =4.769, P =0.000) showed significant decrease during esmolol infusion.On the other hand, central venous pressure [CVP (mmHg, 1 mmHg =0.133 kPa): 9±3 vs.8±3, t =-3.617, P =0.003], diastolic blood pressure (DBP, mmHg: 69± 15 vs.66± 13, t =-2.656, P =0.019), systemic vascular resistance index (SVRI, kPa·s·L-1·m-2:206.8±69.8 vs.206.8±69.8, t =-3.255, P =0.006) were significantly increased during esmolol infusion.No significant difference was found in systolic blood pressure [SBP (mmHg): 120 ± 25 vs.123 ± 18, t =0.678, P =0.509],mean arterial pressure [MAP (mmHg): 86 ± 18 vs.85 ± 14, t =-0.693, P =0.500], global end diastolic volume index [GEDVI (mL/m2): 614 ± 84 vs.618 ± 64, t =0.218, P =0.830], extravascular lung water index [EVLWI (mL/kg):5.99±1.50 vs.5.73±1.14, t =-1.329, P =0.205], central venous oxygen saturation (ScvO2: 0.711±0.035 vs.0.704 ± 0.048, t =-0.298, P =0.773), arterial blood lactate [Lac (mmol/L): 3.1± 0.3 vs.3.0 ± 0.4, t =-0.997, P =0.345],and difference of central venous-arterial carbon dioxide partial pressure [Pcv-aCO2 (mmHg): 4.1 ± 0.9 vs.4.7 ± 0.5,t =1.445, P =0.182] as compared with those before esmolol treatment.Conclusion Heart rate control with esmolol infusion may reduce fluid responsiveness, cardiac function, heart rate and cardiac output without adverse effect on systemic perfusion in septic shock patients.

Nebivolol reduces central blood pressure in stage I hypertensive patients: experimental single cohort study / Nebivolol reduz pressão arterial central em pacientes hipertensos estágio I: estudo experimental de coorte única

CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP) has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients. DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital. METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP and augmentation index) before and after 3 months of using nebivolol. RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2) with large abdominal waist (102.1 ± 7.2 cm). There were significant decreases in peripheral systolic BP (P = 0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083) after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment. CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP. .

CONTEXTO E OBJETIVOS: A avaliação da pressão arterial central (PAc) tem crescido substancialmente nos últimos anos porque as evidências mostraram que PAc central é mais relevante para os desfechos cardiovasculares do que pressão arterial (PA) periférica. Assim, diferentes classes de anti-hipertensivos têm efeitos diferentes sobre PAc apesar de reduções semelhantes na PA braquial. O objetivo foi investigar o efeito do nebivolol, β-bloqueador com propriedades vasodilatadoras, nos parâmetros bioquímicos e hemodinâmicos de pacientes hipertensos. TIPO DE ESTUDO E LOCAL: Estudo de coorte única experimental realizado em ambulatório de hospital universitário. MÉTODOS: Todos os 26 pacientes recrutados foram submetidos à avaliação bioquímica e hemodinâmica (PA, frequência cardíaca, FC, PAc, augmentation index) antes e após três meses usando nebivolol. RESULTADOS: 88,5% dos indivíduos eram do sexo masculino, com média de idade de 49,7 ± 9,3 anos, predominância de sobrepeso (29,6 ± 3,1 kg/m2) e aumento da cintura abdominal (102,1 ± 7,2 cm). Houve diminuição significativa da PA sistólica periférica (P = 0,0020) e diastólica (P = 0,0049), da FC (P < 0,0001) e da PAc (129,9 ± 12,3 x 122,3 ± 10,3 mmHg, P = 0,0083) após o tratamento em comparação aos valores basais. Não houve diferença no augmentation index, nem nos parâmetros bioquímicos antes e após o período de tratamento. CONCLUSÕES: O uso de nebivolol parece estar associado à redução significativa da PAc em hipertensos estágio 1, além da redução da pressão sistólica e diastólica braquial. .